Ultraviolet B-induced inflammation in the rat: a model of secondary hyperalgesia?

Cutaneous inflammation induced by ultraviolet (UV) irradiation in the UV-B range has received significant recent interest as a translational inflammatory pain model. Changes in thermal and mechanical sensitivities in the area of primary hyperalgesia are well documented in both the rat and human UV-B models, but the occurrence of secondary mechanical hyperalgesia is controversial. We investigated the occurrence of secondary mechanical hyperalgesia in the rat UV-B model. Additionally, we investigated whether secondary hyperalgesia was enhanced by heat rekindling of UV-B-irradiated skin as a new rat inflammatory model of sensitisation with an enhanced central contribution. UV-B irradiation (1000 mJ/cm²) induced significant secondary mechanical hyperalgesia and allodynia that peaked at 48 h. Heat rekindling (45 °C stimulus for 5 min) of UV-B-irradiated skin at 24 h further enhanced and prolonged this secondary mechanical hyperalgesia and allodynia, with a peak at 72 h. Heat rekindling also induced a significant mechanical hyperalgesia and allodynia on the contralateral hind paw, further suggesting the contribution of central sensitisation. Our data provide strong evidence for a central contribution in both the rat UV-B pain model and an enhanced contribution in the new model combining UV-B irradiation with heat rekindling. We also elucidate potential differences in the methods used by ourselves and others to obtain mechanical withdrawal thresholds in rats, which may explain the lack of secondary hyperalgesia in the rat UV-B model.     

Further evaluation of the pain stages of change questionnaire: is the transtheoretical model of change useful for patients with chronic pain?

Patient readiness to adopt new beliefs and coping responses to pain may predict response to multidisciplinary or cognitive-behavioral pain treatments that emphasize changes in beliefs and coping behaviors. According to the transtheoretical model of change, individuals go through specific stages in the process of changing maladaptive behaviors. Based on this model, Kerns et al. (1997) (Kerns RD, Rosenberg R, Jamison RN, Caudill MA, Haythornthwaite J. Readiness to adopt a self-management approach to chronic pain: the Pain Stages of Change Questionnaire (PSOCQ). Pain 1997;72:227-234) developed a measure of readiness to adopt a self-management approach to pain problems (the Pain Stages of Change Questionnaire; PSOCQ) and provided preliminary data supporting the validity of the measure. The current study sought to further evaluate the PSOCQ by determining the generalizability of these preliminary findings and the ability of the PSOCQ to classify persons with chronic pain into specific stages of readiness to self-manage pain. One hundred ten patients with diverse chronic pain problems, and 119 patients with fibromyalgia completed the PSOCQ and two measures of pain-related beliefs and coping prior to entry into two separate multidisciplinary pain programs. The internal consistency and concurrent validity of the PSOCQ subscales were largely replicated, supporting the validity of the subscales as measures of readiness to self-manage pain. However, the PSOCQ demonstrated less utility as a tool for classifying individuals into one of four specific stages of readiness to adopt a self-management approach. This result may be due to the classification procedure used in the current study, the characteristics of the samples in the study, specific limitations of the measure, and/or limitations in the applicability of the transtheoretical model of change to patients with chronic pain.     

The value of pupillary dilation in pre-emptive analgesia: is there more to this than meets the eye?

The pupillary dilatation reflex may present an objective method of predicting whether sedated patients require additional analgesia for painful procedures. Behavioural pain assessment tools identify pain only once it has occurred and are unable to guide pre-emptive management. The pupillary dilatation reflex response to a tetanic stimulus has been utilised to assess analgesic requirements in patients under anaesthesia and for those with postoperative pain. This tool appears promising to assess pain in the critically ill; however, a number of questions remain unanswered regarding the influence of sedation on this response. These questions require further exploration before the pupillary dilatation reflex can be widely adopted into clinical practice.In the current issue of Critical Care, Paulus and colleagues investigate whether the need for additional analgesia to prevent pain from endotracheal suctioning can be predicted by measuring the pupillary dilatation reflex (PDR) response to tetanic stimulation in deeply sedated patients [1].This study touches on two important issues: objective pain assessments and pre-emptive analgesia. Pain in the critically unwell can lead to significant physiological and psychological consequences, and may affect patient outcome. Assessing pain in the critically ill is challenging. When patients are unable to self-report, assessment is based on behavioural and physical signs. Unfortunately physiological variables are not predictive of the presence or absence of pain [2], and recommended behavioural tools (Critical Care Pain Observation Tool and Behavioural Pain Scale) [3] only identify patients who are experiencing pain.Procedural pain is an integral component of the pain experience in critical care [4]. This pain is common and poorly managed [5,6], explained in part by the inability of behavioural tools to predict those patients who require additional analgesia for painful procedures. Apart from chest drain removal, only low-grade evidence supports the use of pre-emptive analgesia for procedural pain [3] and over-administering opioids to patients is not without potential consequence [1]. Management at present is limited to either administering analgesia blindly before every procedure or taking a reactionary approach to treat pain after it has occurred. Both of these options are not ideal. The predictive utility of PDR to guide pre-emptive analgesia for painful procedures might be a possible solution to an important clinical question.Physiologists have explored pupillary dilatation in response to noxious stimulus for over 300 years. Loewenfeld summarised this work and her own investigations in the late 1950s [7], and copious literature now exists exploring this phenomenon in adults and children under general anaesthesia [8], in awake volunteers [9], in organ donors [10] and in the postoperative period [11] as a means of assessing analgesic requirements. Larson and Sessler summarised in their editorial other influencing factors that clinicians need to consider when using PDR in pain assessment, including the effect of drugs and technical difficulties such as patient movement [12]. However, there are a number of questions that remain unanswered concerning the use of PDR in sedated patients, which should be considered.Paulus and colleagues are the first group to investigate PDR in response to tetanic stimuli in deeply sedated patients. The mechanism for this reflex differs between the awake and anaesthetised states. PDR is a supraspinal parasympathetic reflex in patients under general anaesthesia [13] but is sympathetically mediated in awake patients [10]. Which mechanism is present in sedated patients is not clear. Does the mechanism differ dependent on the depth of sedation and how does this affect PDR? Recently the PDR response to light has been shown to reduce with increased levels of sedation [14], and this needs to be explored in response to tetanic stimuli as well.Furthermore, pupil size oscillates naturally (pupillary hippus) in the awake state. This is due to the spontaneous fluctuation between the tone and activity of the sympathetic and parasympathetic nervous systems [15]. Drowsiness can influence the frequency and amplitude of pupillary oscillations. Whether different depths of sedation make a similar contribution to pupil size and affect PDR remains elusive. Finally, the influence of different sedative pharmacological agents on the PDR response requires further investigation. Subgroup analysis by Paulus and colleagues did not demonstrate a difference between groups [1]. However, their small numbers warrant more research to exclude this potential influence.The question of how to manage procedural pain in sedated patients is complex. The use of PDR to predict additional analgesic requirements for endotracheal suctioning, in deeply sedated patients, shows promise. The use of a non-invasive, innoculus stimulus in conjunction with PDR potentially provides an objective measure to guide pre-emptive analgesia. However, to make PDR a truly useful clinical tool, further research needs to address some of the questions raised above.     

Perioperative analgesia: a factor in the development of heel pressure ulcers?

This article presents the incidence of heel pressure ulcers after an elective hip or a knee replacement. The majority of patients in the authors' institute receive either a neuraxial block (epidural and/or spinal) or peripheral nerve blocks (femoral and sciatic), depending on the anaesthetist's and surgeon's preference, and the patient's physical status. The past few years have seen increasing use of peripheral nerve blocks for knee replacement surgery. Patients with either the central or peripheral nerve blockade are at an increased risk of developing heel pressure ulcers. This article describes the experience at a tertiary referral centre and, in particular, highlights the risk of developing heel ulcers in patients receiving peripheral nerve blocks. Medical and nursing staff looking after these patients should be made aware of this complication and appropriate measures should be taken to prevent this avoidable complication.     

What is the optimal dose of epinephrine during cardiopulmonary resuscitation in a rat model?

Objective

Because different species may require different doses of drug to produce the same physiologic response, we were provoked to evaluate the dose-response of epinephrine during cardiopulmonary resuscitation (CPR) and identify what is the optimal dose of epinephrine in a rat cardiac arrest model.

Methods

Rat cardiac arrest was induced via asphyxia, and then the effects of different doses of epinephrine (0.04, 0.2, and 0.4 mg/kg IV, respectively) and saline on the outcome of CPR were compared (n = 10/each group). The primary outcome measure was restoration of spontaneous circulation (ROSC), and the secondary was the change of spontaneous respiration and hemodynamics after ROSC.

Results

Rates of ROSC were 9 of 10, 8 of 10, 7 of 10, and 1 of 10 in the low-dose, medium-dose, and high-dose epinephrine groups and saline group, respectively. The rates of withdrawal from the ventilator within 60 minutes in the low-dose (7 of 9) and medium-dose epinephrine groups (7 of 8) were higher than in the high-dose epinephrine group (1 of 7, P < .05). Mean arterial pressures were comparable, but the heart rate in the high-dose epinephrine group was the lowest among epinephrine groups after ROSC. These differences in part of time points reached statistical significance (P < .05).

Conclusion

Different doses of epinephrine produced the similar rate of ROSC, but high-dose epinephrine inhibited the recovery of spontaneous ventilation and caused relative bradycardia after CPR in an asphyxial rat model. Therefore, low and medium doses of epinephrine were more optimal for CPR in a rat asphyxial cardiac arrest model.     

Prophylaxis of phantom pain: is regional analgesia ineffective?

AIM: A recently published randomized study failed to show a significant reduction of phantom limb pain after perioperative epidural analgesia EDA [9]. Since these findings were not supported by previous studies,we conducted an analysis of factors contributing to the results of phantom limb pain prophylaxis. We calculated the efficacy of perioperative EDA as "Number Needed to Treat" (NNT). METHODS: Included studies were retrieved by a medline-search from 1966 to 1999 and published articles on phantom limb pain prophylaxis. First,we analyzed the influence of patient data, type of intervention and study design on the results. Then,we stratified studies in comparable groups and outcome measures. The efficacy of perioperative EDA in phantom limb pain prophylaxis was calculated using NNT's. The outcome criterion in this analysis was "free of phantom limb pain < or = 3 on an analogue scale from 0 ( no pain) to 10 (worst pain) 12 months after amputation". RESULTS: Variations in preoperative pain, start and duration of regional analgesia and the definition of phantom limb pain were associated with different results. After stratifying the results by the above mentioned definition of phantom pain intensity, only time and duration of regional analgesia showed effects on the study results. Pre-, intra- and postoperative EDA was associated with a significant reduction of phantom limb pain 12 months after amputation, NNT = 5,8 (95%-CI 3,2-28,6). However, a reduction of phantom limb pain by postoperative EDA alone could not be confirmed on the basis of the analysed data. CONCLUSIONS: Perioperative EDA has been shown to be an effective prophylaxis of phantom limb pain. The most important differences between studies were the definition of phantom limb pain by intensity ratings. Thus, perioperative EDA does not completely abolish phantom limb pain, but increases the number of patients with a mild form of phantom pain.     

Systematic neonatal pain evaluation in the delivery room: Does it matter?

Neonatal pain assessment in the maternity ward is insufficient and not systematic. The aim of our study was to show that a systematic neonatal pain assessment in the delivery room would led to a 2-fold relative increase in the pain diagnosis rate. We also hypothesised that some overdiagnosed neonates would receive unnecessary acetaminophen treatment. We prospectively included 96 neonates and evaluated all of them with three scales: Neonate Pain and Discomfort Scale (Echelle Douleur et Inconfort du Nouveau-né) (EDIN), reduced Neonatal Facial Coding System (4 items-NFCS) and an attributed Numeric Rating Scale (NRS-11). A systematic assessment led to a 4-fold relative increase in the pain diagnosis rate. The correlation with the scales used were good. Our study did not show an excessive use of acetaminophen treatment.     

Transgenic studies of pain and analgesia: mutation or background genotype?

The application of transgenic (knockout) technology to the study of pain is rapidly expanding. Despite its power, this technique has several shortcomings that complicate the interpretation of the data obtained. Although compensation by other genes is a well recognized problem, issues related to the background genotype of the mutant mice are less well appreciated. This review describes these confounds as they apply to studies of pain and pain inhibition. We show that the 129 and C57BL/6 mouse strains, which provide the default genetic background on which null mutants are constructed, display significant and sometimes extreme phenotypic differences in many assays of nociception, hypersensitivity, and analgesia. Although problems related to the differential responsiveness of the two strains are minimized by placing knockouts onto "pure" 129 and/or C57BL/6 backgrounds, we also illustrate that neither of these strains are particularly representative of inbred mice in general. Procedures to reduce confounds and converging evidence must be used to accurately determine the functions of the targeted genes in pain-related phenomena.     

Psychological factors in chronic pain: a worthwhile undertaking for nursing?

Chronic pain is one of the clearest examples of the complex relationship between the mind, body, spirit, and environment. After decades of research, a growing body of evidence supports the importance of certain psychological factors in the chronic pain experience. This article reviews research related to evaluating the role of depression, personality factors, pain-related beliefs, trauma, and coping style in the chronic pain experience. Understanding and using the findings of this research can improve nursing care of persons with chronic pain.